Current treatment modalities for soft tissue defects due to various pathologies and trauma include autologous grafting and the use of commercially available fillers. However, these treatment methods are associated with a number of limitations, such as donor site morbidity and volume loss over time. As such, improved therapeutic options are needed. Tissue engineering techniques offer novel solutions to these problems through development of bioactive tissue constructs that can regenerate adipose tissue with an appropriate structure and function. The recent advances in the derivation and characterization of hASCs have led to numerous studies of soft tissue reconstruction. In this chapter, we discuss methods in which our laboratory has used hASCs and silk scaffolds for adipose tissue engineering. The use of naturally occurring and clinically acceptable materials such as silk protein for tissue-engineering applications poses advantages with respect to biocompatibility and mechanical and biological properties.